Sequestering subunit and related compositions and methods

Abstract

A sequestering subunit comprising an aversive agent and a blocking agent, wherein the blocking agent substantially prevents release of the aversive agent from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours; a composition comprising a sequestering subunit in releasable form, wherein, optionally, the mechanical fragility of the sequestering subunit is the same as the mechanical fragility of the therapeutic agent in releasable form; a capsule or tablet comprising a sequestering subunit and a therapeutic agent; and a method of preventing abuse of a therapeutic agent.

The invention claimed is: 
     
       1. A pharmaceutical composition comprising:
 a. a sequestering subunit comprising:
 i. a naltrexone core comprising naltrexone on a substrate; and, 
 ii. a coating comprising a hydrophobic material and a surfactant covering the naltrexone core, wherein the ratio of hydrophobic material to surfactant in the coating is about 30:1; and, 
 
 b. an overcoat comprising an opioid agonist covering the sequestering subunit. 
 
     
     
       2. The pharmaceutical composition of  claim 1  wherein the hydrophobic material is a copolymer of acrylic acid and methacrylic acid. 
     
     
       3. The pharmaceutical composition of  claim 1  wherein the hydrophobic material is Eudragit RSPO. 
     
     
       4. The pharmaceutical composition of  claim 1  wherein the surfactant is sodium lauryl sulphate. 
     
     
       5. The pharmaceutical composition of  claim 1  wherein the hydrophobic material is Eudragit RSPO and the surfactant is sodium lauryl sulphate. 
     
     
       6. The pharmaceutical composition of  claim 1  wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone. 
     
     
       7. The pharmaceutical composition of  claim 6  wherein the opioid agonist is morphine. 
     
     
       8. The pharmaceutical composition of  claim 7  wherein the hydrophobic material is Eudragit RSPO and the surfactant is sodium lauryl sulphate. 
     
     
       9. The pharmaceutical composition of  claim 1  wherein the substrate is a sugar sphere. 
     
     
       10. The pharmaceutical composition of  claim 9  wherein the hydrophobic material is a copolymer of acrylic acid and methacrylic acid. 
     
     
       11. The pharmaceutical composition of  claim 9  wherein the hydrophobic material is Eudragit RSPO. 
     
     
       12. The pharmaceutical composition of  claim 9  wherein the surfactant is sodium lauryl sulphate. 
     
     
       13. The pharmaceutical composition of  claim 9  wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone. 
     
     
       14. The pharmaceutical composition of  claim 13  wherein the opioid agonist is morphine. 
     
     
       15. The pharmaceutical composition of  claim 14  wherein the hydrophobic material is Eudragit RSPO and the surfactant is sodium lauryl sulphate. 
     
     
       16. The pharmaceutical composition of  claim 1  wherein the blocking agent prevents the release of at least about 99% of the naltrexone from the sequestering subunit in the gastrointestinal tract for at least about 12 hours. 
     
     
       17. The pharmaceutical composition of  claim 16  wherein the hydrophobic material is Eudragit RSPO and the surfactant is sodium lauryl sulphate. 
     
     
       18. The pharmaceutical composition of  claim 17  wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone. 
     
     
       19. The pharmaceutical composition of  claim 18  wherein the opioid agonist is morphine. 
     
     
       20. The pharmaceutical composition of  claim 1  wherein the blocking agent prevents the release of at least about 95% of the naltrexone from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours. 
     
     
       21. The pharmaceutical composition of  claim 20  wherein the hydrophobic material is Eudragit RSPO and the surfactant is sodium lauryl sulphate. 
     
     
       22. The pharmaceutical composition of  claim 1  wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone. 
     
     
       23. The pharmaceutical composition of  claim 22  wherein the opioid agonist is morphine. 
     
     
       24. The pharmaceutical composition of  claim 1  wherein the blocking agent prevents the release of at least about 99% of the naltrexone from the sequestering subunit in the gastrointestinal tract for at least about 12 hours and prevents the release of at least about 95% of the naltrexone from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours. 
     
     
       25. The pharmaceutical composition of  claim 24  wherein the hydrophobic material is Eudragit RSPO and the surfactant is sodium lauryl sulphate. 
     
     
       26. The pharmaceutical composition of  claim 25  wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone. 
     
     
       27. The pharmaceutical composition of  claim 26  wherein the opioid agonist is morphine. 
     
     
       28. The pharmaceutical composition of any one of  claim 16 ,  20 , or  24  wherein release of naltrexone in the gastrointestinal tract is determined by dissolution testing conducted according to USP26 Chapter <711>using Apparatus 1 (baskets) at 50 rpm, 500 mL of water, 37° C. and high-performance liquid chromatography assay. 
     
     
       29. The pharmaceutical composition of any one of  claim 19 ,  23 , or  27  wherein release of naltrexone in the gastrointestinal tract is determined by dissolution testing conducted according to USP26 Chapter <711>using Apparatus 1 (baskets) at 50 rpm, 500 mL of water, 37° C. and high-performance liquid chromatography assay.